Researchers at McLean Hospital, Belmont, Mass., using a new brain
imaging technique they developed, have identified a key area of the
brain that is underactive in children with attention deficit
hyperactivity disorder (ADHD). The technique, a new form of functional
magnetic resonance imaging (fMRI), also enabled the researchers to show
how Ritalin restored function in ADHD children who were demonstrably
hyperactive - that is, children who had an impaired ability to sit still
during a computerized motion analysis test.

The findings are significant because they provide further evidence
for a biological basis for ADHD and bring new information to the
discussion of Ritalin use in children and the subjectivity with which
ADHD is diagnosed.

The research team, led by Martin Teicher, MD, PhD, director of
McLean Hospital's Developmental Biopsychiatry Research Program,
reported their findings in a recent issue of Nature Medicine.

ADHD is one of the most commonly diagnosed psychiatric disorders in
children. Clinical hallmarks of ADHD are hyperactivity, inattention and
impulsivity.

The McLean study involved six healthy boys with no history of ADHD
or psychiatric disorders, and 11 boys diagnosed with ADHD according to
the standard DSM-IV criteria. All 17 boys also were given a computer
test that uses an infrared motion analysis system to objectively measure
activity, movement and attention. Six of the 11 boys who met DSM-IV
criteria for ADHD were also confirmed to be hyperactive by the objective
computer test.

Using their new fMRI technique, Teicher and his colleagues
identified one area of the brain--the putamen--to which ADHD symptoms
may be closely tied. Long-believed to be important in motor function and
some aspects of attention, the putamen was shown to have diminished
blood flow in the children with ADHD. Further, the researchers found,
the more objectively hyperactive or inattentive the children were, the
greater was their impairment in blood flow to the putamen.

For the six ADHD boys who tested objectively hyperactive, the
researchers found that use of Ritalin enhanced blood flow significantly
in the putamen. However, conversely, for the five ADHD boys who were not
objectively hyperactive, Ritalin decreased blood flow in the putamen
even further.

"This study supports other research that points to the putamen
as an important region of the brain involved in ADHD, and that
diminished blood flow in the putamen may be another way to objectively
diagnose ADHD," said Teicher. "It also shows that Ritalin may
not be effective for all children diagnosed with ADHD using only DSM-IV
criteria. These criteria identify a mixed group of children with similar
behavioral problems, some of whom have an identifiable neurobiological
abnormality and a deficient capacity to sit still and pay attention. But
the DSM-IV criteria are broad and seem to include children with similar
behavioral problems that may arise for other reasons."

The 11 ADHD boys were treated one week at a time with randomly low,
medium and high doses of Ritalin and placebo, and were scanned on each
dose. The six healthy boys were not medicated and scanned only once. The
new fMRI test, unlike conventional MRI, enabled investigators for the
first time ever to study brain blood flow at rest in the boys while on
Ritalin and on placebo, thus allowing them to see which area of the
brain the medication was targeting and whether or not it was working.

"Many children have the capacity to sit still but do not
utilize that capacity. Using our new technique, we found that children
who tested objectively hyperactive had a physiological reason for not
sitting still and that they are the ones who may receive the greatest
benefit from Ritalin," said Teicher.